# Multi-probe minimally invasive endomicroscope

> **NIH NIH R43** · MODENDO INC. · 2023 · $121,255

## Abstract

PROJECT SUMMARY
This project seeks to develop a multi-probe ultrathin endomicroscope to enable high-resolution imaging and
photo-stimulation at multiple sites within currently inaccessible regions of the brain. The instrument will be
amenable to scientific studies in model animals and a stepping stone for future medical instrumentation targeted
at diagnosis and disease treatment in humans.
The company addresses the critical need in the scientific and medical fields for endoscopes that are minimally
invasive, with a cross section in the order of 100μm. The proposed system prototype will be digitally programmed,
contain no moving parts, and simultaneously address multiple probes that penetrate tissue with negligible
damage. The target application is deep brain imaging and photo-stimulation simultaneously in multiple regions
of the brain. The system will enable imaging difficult-to-reach brain areas, such as the brain stem or the olfactory
bulb, with negligible trauma to the animal. The possibility of inserting multiple imaging probes to correlate stimulation
and activity in different regions of the brain could provide new understanding of the connectome and help observe
differences between healthy and diseased brains.
Current endoscopic solutions are appropriate for insertion in large cavities but they produce excessive damage
in applications such as deep brain imaging. This project will create a minimally–invasive, robust, flexible, and
compact prototype for multi-probe endomicroscopy. The key innovation is in achieving the fundamentally thinnest
mechanism to transmit a high information content image in real time and in parallelizing it to multiple brain sites.
The individual probes have a cross-area 10 times smaller than the thinnest existing endoscopes. Further, each
of the probes will be able to deliver multiple functions: 3D imaging with micrometer resolution, fluorescence and
reflection imaging, as well as laser pattern generation for photo-stimulation and ablation.
The imaging approach implements wavefront shaping in various multimode fiber probes simultaneously, using
advanced machine learning and signal processing methods, to generate arbitrary digitally-reprogrammable light
patterns and 3D images. The system uses a spatial light modulator to first calibrate each fiber and then scan
light at high speed, compensating for the inherent modal dispersion and intermodal coupling.
The demonstration of the first in-vivo imaging and optogenetics experiments through a multimode fiber, showing
populations of neurons individually imaged at depth, with subcellular resolution, and with minimal tissue damage,
opens exciting opportunities for expansion and development into mullti-probe multi-modality systems. The
company’s initial focus is on de-risking and validating the use of multimode fiber probes in animal functional
neuro-imaging. The long-term vision is to translate the technology towards medical applications.

## Key facts

- **NIH application ID:** 10898521
- **Project number:** 3R43NS127710-02S1
- **Recipient organization:** MODENDO INC.
- **Principal Investigator:** Antonio Miguel Caravaca Aguirre
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $121,255
- **Award type:** 3
- **Project period:** 2022-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898521

## Citation

> US National Institutes of Health, RePORTER application 10898521, Multi-probe minimally invasive endomicroscope (3R43NS127710-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10898521. Licensed CC0.

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